Herrmann S-M, Adler Y D, Schmidt-Petersen K, Nicaud V, Morrison C, Paul M, Zouboulis Ch C
Institute of Clinical Pharmacology and Toxicology, Department of Clinical Pharmacology, University Medical Center Benjamin Franklin, Freie Universität Berlin, Fabeckstrasse 60-62, 14195 Berlin, Germany.
Br J Dermatol. 2003 Oct;149(4):877-83. doi: 10.1046/j.1365-2133.2003.05640.x.
Gardner syndrome, a phenotypic variant of familial adenomatous polyposis, is characterized by the classical clinical triad of skin and soft tissue tumours, osteomas and intestinal polyposis, but disease patterns with pairs of these findings have also been reported. Different mutations in the adenomatous polyposis coli (APC) gene have been shown to be associated with Gardner syndrome disease phenotypes. A 36-year-old patient presented with multiple epidermal cysts on the face, left ear lobe and neck, and the possible diagnosis of Gardner syndrome was based on the additional findings of two classical osteomas in the left radius and ulna and a cold non-malignant nodule of the thyroid gland. Intestinal polyposis was lacking at the time of examination. Major deletions but not microdeletions were excluded by a cytogenetic analysis with 650 chromosomal bands per haploid set. Systematic sequencing of the entire coding region of the APC gene (> 8500 bp) of the patient and five healthy controls was also performed. As a results, new APC gene polymorphisms were identified in exons 13 [A545A (A/G)] and 15 [G1678G (A/G), S1756S (G/T), P1960P (A/G)]. We also detected D1822V (A/T) which has recently been reported to be potentially related to colorectal carcinoma, and genotyped 194 randomly chosen healthy individuals from the Glasgow area for this as well as for the above variants in exons 13 and 15. Interestingly, of the 194 controls, 112 carried the DD (57.7%), 71 the DV (36.6%), and the remaining 11 (5.7%), including our patient, the VV genotype. It is therefore unlikely that APC D1822V serves as an important marker for colorectal carcinoma. In conclusion, we failed to identify obvious germline candidate mutations in > 8500 bp of the coding region of the APC gene in a patient with multiple epidermal cysts, osteomas and a thyroid gland nodule; major chromosomal deletions were excluded. Therefore, we assume that only the presence of intestinal polyposis is a marker for Gardner syndrome.
加德纳综合征是家族性腺瘤性息肉病的一种表型变异，其特征为皮肤和软组织肿瘤、骨瘤及肠道息肉病这一典型临床三联征，但也有仅出现其中两项表现的疾病模式的报道。已证实腺瘤性息肉病 coli（APC）基因的不同突变与加德纳综合征的疾病表型相关。一名36岁患者面部、左耳耳垂及颈部出现多个表皮囊肿，基于左桡骨和尺骨有两个典型骨瘤以及甲状腺有一个冷性非恶性结节等额外发现，可能诊断为加德纳综合征。检查时未发现肠道息肉病。通过对单倍体组有650条染色体带的细胞遗传学分析排除了主要缺失但未排除微缺失。还对该患者及五名健康对照者的APC基因整个编码区（>8500 bp）进行了系统测序。结果，在外显子13 [A545A（A/G）]和15 [G1678G（A/G）、S1756S（G/T）、P1960P（A/G）]中鉴定出了新的APC基因多态性。我们还检测到了最近报道可能与结直肠癌相关的D1822V（A/T），并对来自格拉斯哥地区的194名随机选择的健康个体进行了该位点以及外显子13和15中上述变异的基因分型。有趣的是，在194名对照者中，112人携带DD（57.7%），71人携带DV（36.6%），其余11人（5.7%），包括我们的患者，携带VV基因型。因此，APC D1822V不太可能作为结直肠癌的重要标志物。总之，在一名有多个表皮囊肿、骨瘤和甲状腺结节的患者中，我们未能在APC基因>8500 bp的编码区鉴定出明显的种系候选突变；排除了主要染色体缺失。因此，我们认为只有肠道息肉病的存在才是加德纳综合征的标志物。
